Objective To investigate the regulatory effect of interaction between extracellular signal-regulated kinase 1/2 (ERK_1/2) and Rho-associated kinase (ROCK) on the neurovascular unit by activating poly (ADP ribose) polymerase-1 (PARP-1) after cerebral infarction.Methods Thirty-five Sprague-Dawley (SD) rats were randomly divided into sham-operation group and middle cerebral artery occlusion (MCAO) group. Each group was further divided into 1 hrs, 3 hrs, 12 hrs, 24 hrs, 3 days, and 7 days subgroups according to the time points when examination was performed after operation. The protein expression levels of ERK_1/2 and ROCK were measured by Western blot. Another 35 SD rats were randomly divided into control group, model group, Fasudil group, U0126 group, and Fasudil+U0126 group, and neurological function, infarct area, and the protein expression levels of ERK_1/2, ROCK, and PARP-1 were measured.Results For the sham-operation group, the expression of total ERK_1/2 and phosphorylated ERK_1/2 (p-ERK_1/2) remained unchanged over time. For the MCAO group, the expression of total ERK_1/2 remained unchanged, while the expression of p-ERK_1/2 first decreased, then increased, and reached the peak level at 24 hrs after operation. The ROCK expression of MCAO group gradually increased over time, reached the peak level at 12 hrs, and then fell. Compared with the control group, the model group had significantly increased expression of p-ERK_1/2, ROCK, and PARP-1 (P<0.05). Compared with the model group, the Fasudil group had significantly reduced expression of p-ERK_1/2 (P<0.05), the U0126 group had unchanged expression of ROCK (P>0.05), and the Fasudil group, U0126 group, and Fasudil+U0126 group, especially Fasudil+U0126 group, had significantly reduced expression of PARP-1 (P<0.05).Conclusions Both ERK_1/2 and ROCK are involved in the brain damage after cerebral infarction. ERK_1/2, as a downstream effective molecule of ROCK, may regulate the expression of PARP-1 together with ROCK and thus adjust the survival of neurovascular unit after cerebral infarction.