Objective: To evaluate the role of G protein-coupled receptor 30 (GPR30) in 17β estradiol-induced inhibition of ketamine-caused neuroapoptosis in the hippocampus of newborn rats and the relationship with phosphorylated extracellular signal-regulated kinase 1/2 (p-ERKl/2). Methods: Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 7 days, weighing 11-18 g, were divided into 4 groups (n=6 each) using a random number table method: control group (group C), ketamine group (group K), 17β estradiol plus ketamine group (group EK), and GPR30 inhibitor G15 plus 17β estradiol plus ketamine group (group G15EK). Ketamine 75 mg/kg (diluted to 0.1 ml in normal saline) was intraperitoneally injected every 24 h for 3 consecutive days in group K. In group EK, 17β estradiol 600 μg/kg was subcutaneously injected and ketamine 75 mg/kg was intraperitoneally injected every 24 h for 3 consecutive days.G15 300 μg/kg and 17β estradiol 600 μg/kg were subcutaneously injected and ketamine 75 mg/kg was intraperitoneally injected every 24 h for 3 consecutive days in group G15EK.The equal volume of normal saline 0.1 ml was intraperitoneally injected instead in group C. The animals were sacrificed at 24 h after the last injection for determination of the expression of cleaved caspase-3, ERK1/2 and phosphorylated ERK1/2(p-ERK1/2) (by Western blot). Results: There was no significant difference in the expression of ERK1/2 in hippocampus among the four groups (P>0.05). Compared with group C, the expression of cleaved caspase-3 was significantly up-regulated, and the expression of p-ERK1/2 was down-regulated in K and G15EK groups (P<0.05). Compared with group K, the expression of cleaved caspase-3 was significantly down-regulated, and the expression of p-ERK1/2 was up-regulated in group EK (P<0.05). Compared with group EK, the expression of cleaved caspase-3 was significantly up-regulated, and the expression of p-ERK 1/2 was down-regulated in group G15EK (P<0.05). Conclusion GPR30 is involved in 17β estradiol-induced inhibition of ketamine-caused neuroapoptosis in the hippocampus of newborn rats, which is related to up-regulating the expression of p-ERKl/2.