Objective To investigate the cerebral protective role of Duzhi pills on ischemic stroke rats and its mechanisms. Methods The healthy male SD rats were assigned to 5 groups: sham group, model group, Duzhi pill low-dose group (1.0 g/kg a day), Duzhi pill high-dose group (2.0 g/kg a day), or argatroban group (positive control). The low-dose and high-dose groups of Duzhi pills were intragastrically administered once a day for 8 d, while the other groups were intragastrically administered with the same amount of normal saline. Except the sham group, the middle cerebral artery occlusion (MCAO) cerebral ischemia-reperfusion model was established by suture method at 0.5 h after intragastric administration on the 8^th day in other groups, and the ischemia duration was 90 min. Argatroban group was given a single dose (3.0 mg/kg) of argatroban via caudal vein at the same time of reperfusion. After 24 h of cerebral ischemia, the area of cerebral infarction, degree of cerebral infarction and neurological function injury were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining and neurobehavioral score, respectively. The levels of inflammatory factors (transforming growth factor-β1 ［TGF-β1］ and interleukin-1β ［IL-1β］) in the brain after cerebral ischemia were detected by enzyme-linked immunosorbent assay (ELISA), and the coagulation indexes were detected by an automatic coagulation analyzer. The scavenging ability of Duzhi pills on free radicals was analyzed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging experiment. Results High-dose Duzhi pills reduced the cerebral infarction area, decreased the deep Nissl staining score of neural cells, and improved the symptoms of neurobehavioral defects in MCAO rats (compared with the model group, all P＜0.01). The levels of IL-1β and TGF-β1 in the ischemic brain tissue of the model group were significantly increased (compared with the sham group, both P＜0.01), while the levels of IL-1β and TGF-β1 in the brain tissue of the rats treated with low-dose and high-dose Duzhi pills were significantly decreased (compared with the model group, all P＜0.01). The coagulation index fibrinogen level in the model group was significantly higher than that in the sham group (P＜0.01), and both low-dose and high-dose Duzhi pills could inhibit the production of fibrinogen (compared with the model group, both P＜0.01). DPPH scavenging test results showed that Duzhi pills could scavenge free radical, the half inhibitory concentration was (1.33±1.11) mg/mL, and the slope of the curve was 1.378±0.145. Conclusion Duzhi pills play a cerebral protective role in ischemic stroke rats. The mechanism may be related to the inhibition of fibrinogen production, the reduction of inflammatory factors (TGF-β1 and IL-1β), and the antioxidant effects.