The present review aimed to clarify determinant cellular and molecular targets of berberine in RA and found that berberine through modulating several signalling pathways involved in the joint inflammation, including PI3K/Akt, Wnt1/β‐catenin, AMPK/lipogenesis and LPA/LPA1/ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells, suppress DC activation and modulate Th17/Treg balance and thus prevent cartilage and bone destruction. This evidence concerns the gene AKT1 and rheumatoid arthritis.