The efficacy of local steroid injection on the extravasation of vesicant anticancer drugs is controversial. In this study, the efficacy of local steroid injection was evaluated macroscopically and histologically in the extravasation models of doxorubicin (DXR), vinorelbine (VNR), and paclitaxel (PTX) in rats. Macroscopically, gross skin lesions were reduced by local steroid injections in rats treated with DXR and VNR. PTX did not cause gross skin lesions in most rats regardless of local steroid injection. Histologically, however, DXR, VNR, and PTX all induced deep tissue lesions such as edema, inflammation, and necrosis. Therefore, the effect of local steroid injection seemed to be minimal. In particular, DXR induced extensive necrosis in the subcutaneous and muscle tissues. VNR-induced skin lesions were milder than those induced by DXR, but had full thickness. Lesions caused by PTX were the mildest. These findings suggest that although local steroid injections could serve a primary role in diluting anticancer drugs and reducing gross skin lesions by their anti-inflammatory effect, they have less ability for suppressing deep-tissue lesions developing over time.