Objective To investigate the protective effects of ulinastatin on express of GRP 78、CHOP and caspase-12, the molecules related to endoplasmic reticulum stress (ERS),after ischemia reperfusion injury in rats.Methods Ninety rats were equally randomized into 3 groups(n=30): Sham group (S group,n=30), Ischemia -reperfusion group (I/R group, n=30), Ulinastatin group (U group, n=30).Focal transient cerebral ischemia model was established with intralu-minal occlusion fo left meddle cerebral artery .Made through 2 hours of temporary middle cerebral artery occlusion , followed with 24 hours of reperfusion .The pathological results were investigated by HE staining and the cerebral injury situation was e -valuated by neurological deficit scores .Infract volume was measured by TTC staining , apoptosis was detected by TdT -medi-ated dUTP and nick end labeling (TUNEL), and expression of GRP78, CHOP and caspase -12 were meastured by western blot.Results Compared with the S group , the number of apoptotic cells were significantly increase in I /R group and U group (P<0.05);infarct volume and expression of GRP -78, CHOP and caspase-12 were significantly increased in I/R group and U group (P<0.05).The infarct volume and the number of apoptotic cells were significantly less in U group than in I/R group ( P<0.05 ) .GRP78 expression was higher in U group than in I/R group ( P<0.05 ) , however CHOP and caspase-12 expression was less in U group than in I/R group (P<0.05).Conclusion Ulinastatin has a protective effect on cerebral ischemia reperfusion injury , which may related to increased GRP 78, decreased CHOP and caspase -12 expres-sion and to inhibition of the ERS -induced apoptosis pathway .