Abstract: The effect of tiletamine on the activity of NOS, NO production, and cGMP content in different brain regions of rat were observed to investigate the modulation of NO/cGMP signal transduction in the molecular mechanisms of general anaesthesia mediated by tiletamine. 168 SD rats were randomly divided into conrol group, high dose tiletamine group(intraperitoneally tilelamine 60 mg/kg) and low dose tiletamine group(ip tilelamine 30 mg/kg )，and each dose group was divided into three sub-groups,eg anesthesia group, recovery groupⅠand recovery groupⅡ. The activity of NOS and production of NO were measured by spectrophotometric analysis, and the cGMP content were measured by radioimmunoassay (RIA) in different brain regions. After administering tiletamine, the activity of NOS in the cerebral cortex, the hippocampus and the thalamus in the anesthesia group were obviously inhibited, and the NO production and cGMP content in abovementioned regions were obviously decreased（compared with control group,P<0.05）. The activity of NOS, NO production and cGMP content in recovery groupⅠat the two dosage were recoverd in different degree, and they were significant recovered（compared with control group, P＞0.05）other than cGMP content in the thalamus (compared with control group, P<0.05) in the recovery groupⅡ. Different dose of tiletamine affected significantly the activity of NOS, NO production and cGMP content in the brain stem, and cerebellum. The anesthesia effects of tiletamine might relate to inhibition of NO/cGMP signal transduction in cerebral cortex, the thalamus, and the hippocampus.