This study explores the effects of apelin on retinal microglial cells in rat models of oxygen-induced retinopathy of prematurity (ROP). Totally, 274 rats were selected for establishing oxygen-induced retinopathy (OIR) models, and 92 healthy rats for control group. OIR rats were assigned into OIR, 10-5 g/L apelin, 10-4 g/L apelin, and 10-3 g/L apelin groups. Immunohistochemistry was employed to determine morphology of microglial cells and cell number. CDllb, ionized calcium-binding adapter molecule 1 (IBA-1), TNF-α, and iNOS mRNA and protein expressions were identified using RT-qPCR and Western blotting, respectively. ELISA was employed to determine the levels of VEGF and glial fibrillary acidic protein (GFAP). The amoeboid microglial cells were found in the OIR and 10-3 g/L apelin groups, while bipolar microglial cells were found in the normal control, 10-5 g/L apelin and 10-4 g/L apelin groups. In the 1, 2, 3, and 4th week after apelin treatment, there were significantly decreased bipolar microglial cells, lower mRNA and protein expressions of CDllb, IBA-1, TNF-α and iNOS, and the levels of VEGF and GFAP in the 10-4 g/L apelin group than in the OIR, 10-3 g/L apelin and 10-5 g/L apelin groups. The differences between the normal control and 10-4 g/L apelin groups are not significant. Compared with the OIR group, the 10-5 g/L apelin and 10-3 g/L apelin groups presented decreased microglial cells and mRNA and protein expressions of CDllb, IBA-1, TNF-α, and iNOS. Appropriate concentration of apelin may reduce retinal microglial cells in a rat model of oxygen-induced ROP.