Objective To observe the effect of electro-acupuncture (EA) intervention on expression of Slit2 and SrGAP1 in rats with focal cerebral infarction and to study the underlying mechanism of EA intervention on neuronal plasticity after cerebral ischemia. Methods Sixty male Sprague Dawley rats were randomly divided into Model group(n=30) and EA group (n=30); and according to elctro-apunture treatment duration, both 2 groups were further randomized into 3 subgroups:0 d(n=10),7 d(n=10), and 14 d (n=10).The middle cerebral arteries of the model group and EA group were embolized for 1.5 hours by suture. Nissl staining, immunofluorescence method and Western blotting analysis were sued to observe the histology and morphology change around the cerebral infarction and to assay the expression of Slit2 and SrGAP1 in the cerebral cortex on the ischemic side on day 0, 7, and 14. Results In comparison with the model group, the neurological score of EA group had no obvious difference on day 0 (P>0.05) and was significantly lower on day 7 and day 14 (P<0.01). Nissl staining results showed that in comparison with the model group, EA group had no obvious difference and both groups had reduced nissl body number, disordered array and brain edema on day 0; even on day 7 the nissl bodies were still disordered in the EA group, but the nissl body number increased obviously; while on day 14 the EA group had increased and well arrayed nissl bodies. Immunofluorescence method and Western blotting analysis showed that the fluorescence intensities and grey levels of rat Slit2 and SrGAP1 had no significant differences between model group and EA group on day 1(P>0.05); but on day 7 and day 14, the fluorescence intensities and grey levels of EA group were significantly higher than those of the model group(P<0.05). In the model group the above values on day 0 were significantly lower than those on day 7 (P<0.05), and those on day 7 were significantly higher than those on day 14 (P<0.05). In the EA group the fluorescence intensities and grey levels on day 0 were significantly lower than those on day 7 (P<0.05), and those on day 7 were significantly higher than those on day 14 (P<0.05). Conclusion Slit2 and SrGAp1 are lowly expressed following focal cerebral infarction on day 0, and EA intervention for one and two weeks can promote their expression and prolong the duration of high expression, subsequently accelerating axonal regeneration and repair, which may be a mechanism of EA therapy for neurological function recovery following cerebral infarction.