MiR-182-5p suppresses expression of Foxo1 that is a protective factor in renal disorders and is up-regulated in systemic lupus erythematosus patients. Thus, we hypothesized that dys-function of miR-182-5p/Foxo1 axis contributed to development of lupus nephritis (LN). Firstly, we investigated the expressions of miR-182-5p and Foxo1 in LN patients and during growth of LN MRL/lpr mice. Then we subjected MRL/lpr mice to the injection of miR-182-5p antagomirs and assessed the effect of miR-182-5p inhibition on renal structure and function. In vitro, we administrated renal cell lines with TGF-β1 to explore the relation between renal fibrosis and miR-182-5p. The level of miR-182-5p was up-regulated in high Chronicity Index patients while the level of Foxo1 was suppressed. The progression of LN in mice was associated with the increased level of miR-182-5p and the decreased level of Foxo1. The inhibition of miR-182-5p ameliorated renal structure and function impairments associated with LN, along with the increased expression of Foxo1. The administration of TGF-β1 in vitro increased the expression of miR-182-5p in renal cells in an overall dose-dependent manner. The current study demonstrated that the expression of miR-182-5p was increased in LN patients, contributing to the suppression of Foxo1 and development of LN.