In this study, we reveal that STAT3 knockdown attenuates the expression of PD-L2, p-LIMK2 and p-cofilin in osteosarcoma, suggesting that VEGFR2 inhibition suppresses migration, invasion and PD-L2 expression by targeting the STAT3 and RhoA-ROCK-LIMK2 pathways. Here, RHOA is linked to osteosarcoma.