Objective To investigate the effects of intranasal administration of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on expressions of nestin and caspase-3 in the perihematomal tissue after intracerebral hemorrhage in rats. Methods A total 36 adult male Sprague-Dawley rats were randomly divided into 3 groups: an HB-EGF group, a control group, and a sham operation group (n = 12 in each group). Then they were further divided into 4-, 7-, and 10-day subgroups (n = 4 in each subgroup). A model of intracerebral hemorrhage was induced by injecting type Ⅳ colagenase. At 1 to 3 days after modeling, the HB-EGF group was intranasaly administrated HB-EGF. The control group was administrated the same volume of saline. The Bederson score was conducted at the corresponding time points and the rats were sacrificed after the forelimb placing test. Immunohistochemistry was used to detect the expression of nestin and caspase-3 in the perihematomal tissue. Results The sham operation group did not have neurological deficits. The Bederson scores (P < 0. 05) and the result of forelimb placing test (al P < 0. 01) at day 4 and 7 in the HB-EGFgroup were better than those in the control group. There were no significant differences at day 10. At day 4, 7, and 10, the number of nestin positive cels in the perihematomal tissue in the HB-EGF group was significantly more than that in the control group (al P < 0. 05), and the number of caspase-3 positive cels was less than that in the control group (al P < 0. 01). Conclusions Intranasal administration of HB-EGF can improve the early neurological function, upreguate the nestin expression and downregulate the caspase-3 expression in the perihematomal tissue after intracerebral hemorrhage in rats, indicating that intranasal administration of HB-EGF may promote the proliferation of precursor cels and decrease cel apoptosis in the perihematomal tissue.