It has been shown that injecting a suspension of IFN‐γ‐secreting tumor cells results in their rejection. This effect has been attributed to IFN‐γ preventing tumor stroma formation but not to a direct effect on the cancer cells. However, it is not known, which influence IFN‐γ has on tumors with an established stroma. To address this question, the plasmacytoma cell line J558L was transduced with a vector allowing doxycycline‐inducible IFN‐γ gene expression. After the injection of the tumor cells into mice, IFN‐γ was induced at different time points. Tumors did not grow when inducing IFN‐γ immediately after tumor cell inoculation, while approximately half of the tumors were rejected when IFN‐γ was induced in early established tumors within 2 weeks. Induction of IFN‐γ 2–3 weeks after tumor cell inoculation was less efficient (0–17% rejection). IFN‐γ induction in established tumors led to a reduction of CD146+ endothelial cells and massive necrosis. Together, we show that vascularized tumors can be rejected by local IFN‐γ expression, but that rejection of established tumors was less efficient over time. This suggests that transplanted tumors became less susceptible to local IFN‐γ treatment the better they are established.