Objective To explore the effect of R-(-)-α-methylhistamine (RAMH) on the isoflurane exposure induced neuronal apoptosis and memory impairment in the developing rats. Methods Twenty-eight 6-7 days SD rats were randomly divided into four groups:control (CON) group (intraperitoneal injection of 5% glucose[0.1 mL/10 g], isoflurane (ISO) group (intraperitoneal injection of 5% glucose[0.1 mL/10 g] and then exposure to 1.6% ISO for 6 hours), RAMH group (intraperitoneal injection of RAMH[10 mg/kg], and RAMH+ISO group (after intraperitoneal injection of RAMH[10 mg/kg] for 30 min, then exposure to 1.6% ISO for 6 hours). Morris water maze test was employed to investigate the learning and memory ability. Immunofluorescence and Western blotting were employed to determine the neuronal apoptosis and p53 expression in the hippocampus of rats, respectively. Results Morris water maze test showed that the time in the target quadrant of ISO group was significantly shorter than that of CON group (n=7, P<0.01), while the time of RAMH+ISO group was significantly longer than the ISO group (n=7, P<0.05). The number of apoptotic neurons in hippocampus in the ISO group was significantly increased compared with either the CON group or the RAMH+ISO group (n=5, both P<0.01). Compared with the CON group, the expression of p53 protein in hippocampus was significantly increased in the ISO group (n=6, P<0.01), while p53 expression in the RAMH+ISO group was significantly lower than that in the ISO group (n=6, P<0.01). Conclusion RAMH can ameliorate ISO exposure induced neuronal apoptosis and memory impairment in the developing rat.