Objective: This study aims to explore the molecular mechanism of macrophages and gamma delta-T cells in the ZOL drug-induced osteonecrosis of jaws based on the IFN-gamma involved osteoblast differentiation signaling pathway. Results: The number and apoptotic rate of CD11b+Gr1hi cells and gamma delta-T cells in the ONJ group were significantly higher. The TNF-alpha, IL-1 beta, IFN-gamma, CCL3, CCL4, IL-12 and IL-13 levels were significantly higher in the ONJ group. The expression of CTSK and FGFR3 was lower in the ONJ group, but was higher in the NF-kappa B and ERBB2IP group. Conclusion: The proliferation of macrophages and gamma delta-T cells promote the inflammation in ZOL-induced jaw necrosis. Methods: A total of 20 patients with osteonecrosis of the jaw from January 2016 to March 2018 were collected and assigned into the observation group, while 20 healthy subjects were assigned into the control group. Furthermore, 40 SD rats were selected and assigned into observation group, while 10 non-treatment SD rats were selected and assigned as controls. The distribution and proportion of CD11b+Gr1hi cells and gamma delta-T cells in the necrotic tissues of the jaw were analyzed. Then, the TNF-alpha, IL-1 beta, IFN-gamma, CCL3, CCL4, IL-12 and IL-13 levels were measured. Afterwards, the expression of CTSK, FGFR3, NF-kappa B and ERBB2IP in the necrotic tissues of the jaw in the animal models were analyzed.