Objective To explore the mechanism of triptolide reducing oxygen glucose deprivation / reoxygenation (OGD/ R)-induced SH-SY5Y cell injury via the NogoA/ RhoA/ ROCK signaling pathway. Methods The effect of various triptolide concentrations on SH-SY5Y cell proliferation was assessed by CCK8 assays to select the optimal concentration. Cells were divided into normal control, model, triptolide (1 nmol / L) treatment and fasudil (15 μg / mL) treatment groups. Cell proliferation was assessed by CCK8 assays. A JC-1 assay was used to measure the mitochondrial membrane potential. NogoA, ROCK2 and GAP43 expression was detected by immunofluorescence staining. GAP43, PSD95, NogoA, NgR, RhoA and ROCK2 expression was detected by Western blot. Results CCK8 assays showed that the optimal concentration of triptolide was 1 nmol / L. Cell proliferation and the mitochondrial membrane potential of the model group were significantly lower than those of the control group ( P< 0. 001). Compared with the control group, GAP43 and PSD95 expression was decreased and NogoA, NgR, RhoA and ROCK2 expression was increased in the model group (P<0. 001). Both triptolide and fasudil increased cell proliferation (P<0. 001) the and mitochondrial membrane potential (P<0. 001), upregulated GAP43 and PSD95 expression (P<0. 05), and downregulated NogoA, NgR, RhoA and ROCK2 expression (P<0. 001). Conclusions Triptolide may alleviate OGD/ R-induced SH-SY5Y cell injury by inhibiting the NogoA/ RhoA/ ROCK signaling pathway.