Abstract: Objective To investigate the effect of proge sterone(PROG)on the expression of inducible nitric oxide synthase(NiOS)and caspase-3 in the cortex after traumatic brain injury(TBI)and to study the neuro protective effects and molecular mechanism of progesterone on TBI in rats.Methods Healthy male Spraque Dawley rats were divided at random into three groups:false operative group,TBI group and PROG treated group.The TBI of rats was duplicated with the miproved Feeneys method.The rats in the three groups were killed at 6,24,48,72,and 144 hours after the injury.The expression of iNOS and caspase-3 were examined by mimunohistochem istry.Results At the time of 6,24,48,and 72 hours after the injury,the expression of NiOS and caspase 3 in the PROG treated group were 11.62±1.52,21.38±1.41,12.94±2.73,9.42±1.71,and 12.27±1.35,20.57±2.92,16.54±1.45,10.47±1.39,respectively,and were distinctly less than those of the TBI group(18.24±1.93,43.17±3.58,20.13±3.81,13.82±2.56,and 24.56±2.71,38.23± 3.36,27.83±2.68,14.23±2.83).There were significant differences between the TBI group and the PROG treated group in the number of NiOS and caspase-3 positive cells at 6,24,48,and 72 hours after injury(P<0.05 for all).Conclusion PROG has protective effect on TBI that may relate to inhibition of NiOS activity,down regutation of caspase 3 expression.