Objects: Immunotherapy is an important method to restrain and eradicate tumor cells. CD40-CD40 ligand (CD40L) system plays a critical role in the immunotherapy of tumors including lymphoma. CD40L promotes the induction of tumor-specific T cells and a number of cytokines that induce the change of tumor microenvironment. The objective of this study is to discover some working principles of tumors immunotherapy. Methods: We have used the recombinant adenovirus encoding murine CD40L (AdvmCD40L) to infect the murine B lymphoma cells (A20) in vitro and in vivo. Costimulatory molecules CD80 and CD86 expression of A20 cells was assessed by flow cytometry. We observed direct antitumor effect and prophylactic antitumor protection effect of AdvmCD40L by measuring the tumor size of lymphoma model (A20) in BALB/c mice. 48 hour after AdvmCD40L was injected, the tumor was removed to administer immunohistochemistry experiment for detecting VEGF expression and micro vessel density counting (MVD) in A20 tumor. Results: After infection with AdvmCD40L, A20 cells up-regulated several T-cell costimulatory molecules (CD80, CD86) expression and VEGF expression is also up-regulated in tumor tissue. Inhibition of tumor growth was observed in mice with pre-existing tumors treated with AdvmCD40L. Mice vaccinated with irradiated A20 cells transduced with AdvmCD40L are protected against A20 tumor cells. Conclusions: These results show that genetic modification of tumor B cells with CD40L can be a useful strategy to promote systemic immunity against B-cell malignancies and provide an in vivo system to allow for additional evaluation and refinement of this approach. And CD40L can stimulate angiogenesis by vascular endothelial growth factor (VEGF) in association with immune cells recruitment.