Departs from the internal carotid artery at the side of the optic nerve cross and pulls straight out to the side, away from the midline over the part of the underside of the brain called the insula border (limen insulae) and into the space between the underside of the frontal lobe and the temporal lobe. The artery - now as the bark trunk of the middle cerebrum artery - then appears on the island (insula) at the base of the lateral furrow, winds backwards and emits a large number of radiating lateral branches which together supply almost the entire outer hemisphere surface. The exception is the actual edge zone towards the inside of the hemisphere where the supply is taken over by the anterior and posterior cerebrum arteries.

After the departure of the internal carotid artery and before the middle cerebral artery (pars sphenoidalis) reaches the insula, it emits as if in a row, 5 - 10 narrow initially unbranched arteries which penetrate through the anterior vascular inlet (substantia perforata anterior) and straight up into the brain tissue above it. These are the anterior external central/perforating cerebral arteries (thalamo-striat, lenticulo-striata artery, etc.) that supply the deep parts of the large brain, i.e. parts of the thalamus, the knee of the inner nerve fibre capsule, its posterior, neck and temporal parts, the shell nucleus and the caudal nucleus. Clots or bleeding in one or more of the deep cerebral arteries are common causes of stroke with severe functional disorders within the opposite half of the body.

Once out on the insula (pars insularis), the artery winds in the depths of the lateral furrow in an intricate curved way. Here it also usually divides into its three final main branches: the anterior, middle and posterior main stem.

When these main stems reach the surface of the free cortex, the entire increasingly finely branched vascular mass is called the "middle cerebrum artery terminus" (pars terminalis).

An injury immediately after departure from the internal carotid artery causes very severe functional disorders - paralysis and loss of sensation - in the entire opposite half of the body. In the case of bleeding, the condition is life-threatening. In addition, there is loss of (blindness in) one half of the visual field in both eyes opposite the side where the injury is located (right- or left-sided homonymous hemianopsia), and that the eyes look to the side where the injury is located; gaze direction palsy.
If the injury is in the left hemisphere of the brain, the sufferer suffers from extensive (global) speech paralysis (aphasia). A right-sided injury gives a severe left-sided neglect.

The injury picture in a stroke that involves the middle cerebrum artery varies depending on where in the vessel and its branches the stop/bleeding is located.