Objective: To study the effects of MIPO and ORIF on stress degree and bone metabolism activity in patients with middle humeral shaft fractures. Methods: Patients with middle humeral shaft fractures who received surgical treatment in Mianyang Orthopedic Hospital between June 2010 and October 2015 were enrolled and randomly divided into MIPO group and ORIF group who were treated with minimally invasive plate oateosynthesis and open reduction internal fixation respectively. Before surgery as well as 1 day and 3 days after surgery, serum was collected to determine the contents of stress response molecules and bone metabolism markers. Results: 1 day and 3 days after surgery, serum stress molecules PGE2, CRP, NE and E as well as bone resorption markers TRACP-5B, β-CTX, RANK and RANKL contents of both groups were higher than those before surgery while bone formation markers BGP, BALP, PINP and OPG contents were lower than those before surgery; serum stress molecules PGE2, CRP, NE and E as well as bone resorption markers TRACP-5B, β-CTX, RANK and RANKL contents of MIPO group were lower than those of ORFI group while bone formation markers BGP, BALP, PINP and OPG contents were higher than those of ORFI group. Conclusion:Compared with ORIF, MIPO for middle humeral shaft fractures can reduce stress response degree and improve bone metabolism.