Objective To investigate the effect of propofol on cerebral ischemia-reperfusion injury in rats through the Rho / Rho kinase signaling pathway. Methods One hundred SD rats were divided into control, model, and propofol low, medium, and high dose (20, 40, and 80 mg / kg) groups. Rats in the model and propofol low, medium, and high dose groups were used to establish a cerebral ischemia-reperfusion injury model. After successful modeling, rats in propofol low, medium, and high dose groups were administered the corresponding dose of propofol and rats in control and model groups were administered the same volume of normal saline for 4 weeks. Then, each rat was scored for neurological deficits, stickers were removed, and balance beam walking experiments were performed. Pathological scores in the hippocampus of rats were calculated. Rho and Rho kinase mRNA and protein levels were determined in rat brain tissue. Results The neurological deficit score, bilateral sticker removal time, balance beam time, pathological score of the hippocampus, and Rho and Rho kinase mRNA and protein expression levels in the model group were significantly higher than those in the control group (P<0. 05). The neurological deficit score, bilateral sticker removal time, balance beam time, pathological score of the hippocampus, and Rho and Rho kinase mRNA and protein expression levels in all propofol groups were significantly lower than those in the model group (P<0. 05). With the increase of the propofol dose, the neurological deficit score, the time of side sticker removal, balance beam time, pathological score of the hippocampus, and Rho and Rho kinase mRNA and protein expression levels were decreased gradually and dose-response relationships were obvious (P< 0. 05). In the control group, neuronal cells were intact with a normal structure, clear staining, and oval nucleus in the center. In the model group, a large number of necrotic neurons were seen with obvious cell loss and nuclear pyknosis. In the high dose propofol group, a small number of necrotic neuronal cells were seen, the neuronal cell structure was relatively complete, and the nuclei of neurons were oval in the center. Compared with the model group, the numbers of necrotic neurons were decreased in middle and low dose propofol groups, but the meridians were loose and disordered, the nucleus exhibited pyknosis, and loss was obvious. Conclusions Propofol reduces neurological damage in rats with cerebral ischemia-reperfusion injury. The mechanism is related to inhibition of Rho and Rho kinase mRNA and protein expression by propofol and thus inhibition of activation of the Rho / Rho kinase signaling pathway.