In 1656, Ferdinand II of Tuscany invited him to the professorship of theoretical medicine at the University of Pisa. There Malpighi began his lifelong friendship with Giovanni Borelli, mathematician and naturalist, who was a prominent supporter of the Accademia del Cimento, one of the first scientific societies. Malpighi questioned the prevailing medical teachings at Pisa, tried experiments on colour changes in blood, and attempted to recast anatomical, physiological, and medical problems of the day. Family responsibilities and poor health prompted Malpighi's return in 1659 to the University of Bologna, where he continued to teach and do research with his microscopes. In 1661 he identified and described the pulmonary and capillary network connecting small arteries with small veins, one of the major discoveries in the history of science. Malpighi's views evoked increasing controversy and dissent, mainly from envy, jealousy, and lack of understanding on the part of his colleagues. (see also Index: pulmonary circulation)
Hindered by the hostile environment of Bologna, Malpighi accepted (November 1662) a professorship in medicine at the University of Messina in Sicily, on the recommendation there of Borelli, who was investigating the effects of physical forces on animal functions. Malpighi was also welcomed by Viscount Francavilla, a patron of science and a former student, whose hospitality encouraged him in furthering his career. Malpighi pursued his microscopic studies while teaching and practicing medicine. He identified the taste buds and regarded them as terminations of nerves, described the minute structure of the brain, optic nerve, and fat reservoirs, and in 1666 was the first to see the red blood cells and to attribute the colour of blood to them. Again, his research and teaching aroused envy and controversy among his colleagues.
After four years at Messina, Malpighi returned in January 1667 to Bologna, where, during his medical practice, he studied the microscopic subdivisions of specific living organs, such as the liver, brain, spleen, and kidneys, and of bone and the deeper layers of the skin that now bear his name. Impressed by the minute structures he observed under the microscope, he concluded that most living materials are glandular in organization, that even the largest organs are composed of minute glands, and that these glands exist solely for the separation or for the mixture of juices.
Malpighi's work at Messina attracted the attention of the Royal Society in London, whose secretary, Henry Oldenburg, extended him an invitation in 1668 to correspond with him. Malpighi's work was thereafter published periodically in the form of letters in the Philosophical Transactions of the Royal Society. In 1669 Malpighi was named an honorary member, the first such recognition given to an Italian. From then on, all his works were published in London.
At the peak of his fame, Malpighi could have left his tiring medical practice and research to accept one of the many highly remunerative positions offered to him. Instead, he chose to continue his general practice and professorship. These years at Bologna marked the climax of his career, when he marked out large areas of microscopy. Malpighi conducted many studies of insect larvae--establishing, in so doing, the basis for their future study--the most important of which was his investigation in 1669 of the structure and development of the silkworm. In his historic work in 1673 on the embryology of the chick, in which he discovered the aortic arches, neural folds, and somites, he generally followed William Harvey's views on development, though Malpighi probably concluded that the embryo is preformed in the egg after fertilization. He also made extensive comparative studies in 1675-79 of the microscopic anatomy of several different plants and saw an analogy between plant and animal organization. (see also Index: silkworm moth)
During the last decade of his life Malpighi was beset by personal tragedy, declining health, and the climax of opposition to him. In 1684 his villa was burned, his apparatus and microscopes shattered, and his papers, books, and manuscripts destroyed. Most probably as a compensatory move when opposition mounted against his views, and in recognition of his stature, Pope Innocent XII invited him to Rome in 1691 as papal archiater, or personal physician, such a nomination constituting a great honour. In Rome he was further honoured by being named a count, he was elected to the College of Doctors of Medicine, his name was placed in the Roman Patriciate Roll, and he was given the title of honorary valet.