Trans-resveratrol (Res) is a well-known natural stilbene frequently found in grapes which have been reported to possess antioxidant, anti-cancer activities and inhibited COX-2 expression. MicroRNAs (miRNAs) are short endogenous non-coding RNAs involved in the regulation of mRNA stability and protein synthesis. In our research, resveratrol isolated from Vitis heyneana Roem. & Schult Vitis heyneana was observed to suppress lipopolysaccharides (LPS)-induced COX-2 expression in Raw264.7 cells in a dose dependent manner. Using qPCR it was revealed that LPS induced the expression of miR-25, miR- 125a, miR-125b, miR-146a-5p, miR-146a-3p and miR-455. However, we only observed miR-146a-5p expression significantly decreased in resveratrol compared to untreated-control group. In addition, resveratrol abrogated the effect of miR-146a-5p mimic induced-COX-2 expression in Raw264.7 cells. Taken together, this study demonstrated for the first time the involvement of miR-146a-5p in resveratrol inhibited LPS-induced COX-2 expression in Raw264.7 cells