Aim To investigate the effect of down-regulation of miR-92a on the secretion of inflammatory mediators and lipid accumulation induced by oxidized low density lipoprotein (ox-LDL) in RAW264.7 cells and its mechanism.Methods RAW264.7 cells were treated with ox-LDL of different concentrations (0,5, 0,0 mg/L) for 24 hours or with 100 mg/L ox-LDL for 0,2 and 24 hours respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the effect of ox-LDL on the expression of miR-92a. A RAW264.7 cell line with low expression of miR-92a was established and treated with 100 mg/L ox-LDL. Effects of down-regulation of miR-92a expression on expressions of inflammatory factors inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and IL-1β, lipid accumulation and expressions of signal transducer and activator of transcription-3 (STAT3) signal pathway-related proteins p-STAT3 and STAT3 in RAW264.7 cells induced by ox-LDL, were detected by qRT-PCR, oil red O staining, nitric oxide (NO) fluorescence probe (DAF-FMDA) and Western blot. A RAW264.7 cell line with low expressions of protein inhibitor of activated STAT3 (PIAS3) and miR-92a was established and treated with 100 mg/L ox-LDL. The effects of silencing PIAS3 expression on inflammatory factors, lipid accumulation and STAT3 signaling pathway were observed in RAW264.7 cells with low expression of miR-92a induced by ox-LDL. TargetScan software prediction and dual luciferase reporting experiment were used to verify the target relationship between miR-92a and PIAS3. Results With the increase of the action time and concentration of ox-LDL, the expression of miR-92a was increased in RAW264.7 cells. The dual luciferase reporting experiment confirmed that PIAS3 was the target gene of miR-92a. After ox-LDL treatment, the expressions of miR-92a, iNOS, IL-6, IL-1β and p-STAT3 were increased, NO release and intracellular lipid droplets were increased in RAW264.7 cells, while the expression of PIAS3 was decreased. This regulatory effect could be inhibited by anti-microRNA-92a, and the inhibition of anti-microRNA-92a could be restored after PIAS3 silence. Conclusion Down-regulation of miR-92a can inhibit ox-LDL induced secretion of inflammatory mediators and lipid accumulation in RAW264.7 cells by regulating PIAS3.