The use of tobacco products has continued for many years, with Nicotine implicated as its major psychoactive component. This study investigated the effects of tobacco smoke on the microarchitecture of the superior colliculus (SC) of adult wistar rats, and its effects on some enzymes. Adult wistar rats with an average weight of 219.5 g were randomly divided into a control and an experimental group; and subgrouped into 2, with respect to sex. The experimental group was exposed to smoke from a completely burnt cigarette, containing 0.735 g tobacco, once daily, while those in the control group inhaled smoke from cotton wool. The rats were sacrificed on days 7, 14 and 21. SC was processed for both histological and enzyme studies. The histological findings showed varying degrees of distortion in the architecture of SC, reduction in number of cells, vacuolations, degenerative changes, and a progressive reduction in the distribution of Nissl bodies in the experimental group. These changes are a result of the increased activity of these enzymes in the SC of the experimental animals which had higher values of Alkaline phosphatise (ALP), Lactate dehydrogenase (LDH).