Objective To investigate the difference in efficacy between doxorubicin released by 41 ℃ and 43 ℃ mild hyperthermia (MH) triggered-pegylated liposomal doxorubicin (PLD) for the treatment of rabbit VX2 tumor. Methods Twelve rabbits with VX2 tumor transplanted into the superficial muscle of the hind limb were randomly assigned to 2 groups, i.e. the 41 ℃ MH+PLD group (n=6) and the 43 ℃ MH+PLD group (n=6). To achieve complete tumor remission, multiple high-dose administrations (5 mg/kg, once per week for 3 weeks) were given by intravenous injection. An embedded ultrasound tumor hyperthermia instrument was used to perform local MH at tumor sites for 30 min. Results At the endpoint, the 41 ℃ MH+PLD group had lower vascularization index, tumor weight, and levels of GOT, LDH and CPK in peripheral blood as compared with the 43 ℃ MH +PLD group. Conclusion In comparison with 43 ℃ MH for 30 min, 41 ℃ MH for 30 min plus PLD can significantly improve the antitumor efficacy, and reduce the systemic toxicity.