Objective To investigate the proper dose of propofol injected intraperitoneally (i.p.)in neonatal rats and to study the regional distribution of propofol at different doses in the neonatal brain. Methods Part I:Sixty postnatal 7-day-old rats were randomly divided into 5 groups, which received different doses of propofol injected i.p.The behavior, anesthetic intervals and arterial blood gas were recorded. Part Ⅱ:Twenty neonatal rats were randomly divided into 2 groups:anesthesia group (group A) and sedation group (group S), and were injected propofol i.p. at the proper dose according to the results of Part I. Rats were decapitated when they reached the ideal anesthesia depth. The regional concentration of propofol in different regions of the brain was examined by high performance liquid chromatography. Results 25 mg/kg propofol i.p. was the sedate dose for neonatal rats, while 75 mg/kg i.p. was the anesthetic dose. In the group S, the concentration of propofol in the thalamus was significantly higher than in other regions (P<0.05), while in the group A, the concentrations of propofol in the frontal and parietal cortex were obviously lower, and the concentrations of propofol in the hippocampus and cingulate gyrus were obviously higher than that in other regions (P<0.05). Conclusions Propofol is a suitable anesthetic for neonatal rats and its distribution in the brain is quite different when given at different doses.