When tobacco is smoked, chewed or snuffed, nicotine is absorbed by the lungs or mucous membrane and quickly moved into the bloodstream, where it is circulated throughout the brain. In fact nicotine is highly dangerous to be consumed in any form. The present study was conducted to know the adverse effects of nicotine on the platelet aggregation in cerebral microvessels of mice. Male mice of average weight 33 g were injected with Saline (control) or Nicotine (1 mg/kg, 0.1 ml/10 g) one hour before the experiment. Animals were anaesthetized and trachea was intubated. Craniotomy was performed and a window was opened on the skull. Layer of dura was removed. Brain surface microvessels were exposed and animal was placed on the microscope stage. Microscope was connected to a monitor and VCR to record all events. Exposed brain surface was continuously irrigated with ACSF solution. After the body temp was maintained at 37? C, Sodium fluorescein (2%, 0.1 ml/10 g) was injected i.v. through tail injection. High intensity mercury light was switched on to induce photochemically induced platelet aggregation. Appearance of the 1st platelet aggregation and total blood flow stop were timed in seconds. Our results showed that in the animals treated with nicotine, venule did not show any alteration in the platelet aggregation timings in comparison to the controls. But in arterioles platelet aggregation timings were significantly accelerated (P<0.001) in nicotine treated animals. [(Control: venule 1st aggregation 22.87 ± 1.45, flow stop 161.25 ± 19.9; Arteriole: 1st aggregation 104.37 ± 19.64, flow stop 167.25 ± 23.54; Nicotine: venule 1st aggregation 23.57 ± 4.79, flow stop 142.15 ± 25.9 Arteriole: 1st aggregation 50.0 ± 13.08, flow stop 100.71 ± 33.70)]. Data shows the adverse influence of nicotine on the susceptibility to thrombosis in the arterioles, in vivo. The enhanced initiation of thrombosis activity may be attributed to the facilitated damage to the arteriolar endothelium caused by nicotine.