Objective:To investigate the biological effects of corticotomy-induced micro-environment around orthodontic teeth on macrophages. Methods:A total of 60 male Wistar rats were randomly divided into the experimental group(TM+CO)and control group(TM)with each group of 30 rats. The rats in each group were sacrificed after 3,5,7,14 and 21 days for tissue collection and assessments. Micro-CT examination was performed to acquire bone mineral density(BMD)around the upper left first molars,to analyze the change of bone remodeling. Morphological changes of periodontal tissues and the expression of CD68,CD11b,CD86,CD163-positive cells were determined by immunohistochemistry. A total of 112 male C57BL/6 mice of eight-week old were randomly divided into the corticotomy group and the vehicle group. The mice in each group were sacrificed after 3,5,7,14,21,28 and 42 days for tissue collection and co-culture. The relative mRNA expression of CD11b,CD68,IL-6,IL-1β,IL-10 and Arg-1 were respectively evaluated by RT-PCR. The protein change of p65 and STAT3 phosphorylation were detected by Western blot. Results:The value of BMD in both groups decreased significantly at the early stage and it was more obvious in the TM+CO group(P < 0.05). Meanwhile,the immunohistochemistry data showed that the expressions of CD68,CD11b,CD86,CD163-positive cells in the TM+CO group were all significantly increased compared with those in the TM group at day 3(P < 0.05). The real-time PCR analysis showed that the mRNA expression levels of CD11b and CD68 in macrophages were significantly higher in the corticotomy group than those in the vehicle group(P < 0.05);they increased from day 3 to day 14 and then declined. Moreover,the mRNA expression levels of M1 marker,TNF-α,IL-1β and M2 marker,IL-10,Arg-1 were significantly higher in the corticotomy group compared with those in the vehicle group(P < 0.05);they increased up to day 14 and then declined. Western blot analysis showed that the level of p65 was upregulated after co-culture with condition medium of maxilla in the corticotomy group early on day 5 and day 7,while the level of phosphorylated STAT3 was upregulated on day 7 and day 14 when compared with those in the vehicle group(P < 0.05). Conclusion:The activation of NF-κB and JAK-STAT signaling pathways may play an important role in corticotomy induced infiltration and polarization of macrophages and thereby influenced bone density and consequent orthodontic tooth movement.