Objective To investigate the protective effect of a mutant of acidic fibroblast growth factor (MaFGF) against cerebral ischaemia-reperfusion injury in rats. Methods Sixty male Sprague–Dawley rats were randomly divided into six groups as follows: sham-operated group, untreated group, 20 μg/kg, 40 μg/kg and 80 μg/kg MaFGF-treated groups and also the positive control group. Cerebral ischaemia-reperfusion injury was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Different dose of MaFGF were infused intravenously at 1 h after middle cerebral artery (MCA) occlusion. Nimodipine was used as positive control. The behaviour deficit score, brain-infarcted area, brain oedema degree, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected at 24 h after reperfusion. Results The results showed that MaFGF at the dose of 20 μg/kg, 40 μg/kg and 80 μg/kg significantly alleviated brain injury. Compared to untreated group, the behaviour deficits were much less severe, the brain oedema alleviated obviously, the MDA contents decreased and SOD activity increased dramatically in MaFGF-treated groups respectively. The efficacy of MaFGF was similar to that of nimodipine. Conclusion The results demonstrate that MaFGF has neuroprotective effect against brain injury resulting from focal ischaemia-reperfusion in Sprague–Dawley rats.