Aims: To investigate the role of Slit2 and Robo1 during the vascular disease of Polymyositis (PM) / dermatomyositis (DM). Background: PM and DM are nonsuppurative inflammatory myopathies that mainly invade the skeletal muscles. Objective: This study attempted to explore the specific mechanism of Slit2/Robo1 signaling pathway proteins during the vascular disease of PM/DM. Methods: The mRNA expressions of Slit2 and Robot in the muscle tissue were detected by RT-qPCR between newly-diagnosed PM/DM patients and healthy controls. The number of Slit2 and Robo1 positive cells in the serial sections of muscle paraffin tissues was measured by immunohistochemistry in 10 patients with PM, 10 patients with DM and 20 healthy controls. Results: The study results revealed that the mRNA expressions of Slit2 and Robo1 in muscle tissue in the PM and DM groups were higher than that in the control group (P<0.05). The positive expression rates of Slit2 and Robo1 in muscle tissue in the PM and DM groups were 80.0%, 80.0%, 70.0% and 70.0%, respectively. The difference was statistically significant (P<0.001), when compared to the control group (the positive expression rates were 0% and 10%, respectively). Conclusion: The activation of the Slit2/Robo1 signaling pathway is an important mechanism leading to the development of PM/DM.