It is worth mentioning that 0.5 mg/kg E2 had no effect on depressive‐like behaviours, but 10 mg/kg (20 times the dose of female mice) E2 caused significant improvement in depression of the male mice, suggesting that the endogenous E2 levels between female and male mice are different, resulting in the different regulatory intensities on inflammatory factors and IDO1 activity. Here, IDO1 is linked to depressive disorder.