Objective To investigate the cerebral protection effect of downregulation of thioredoxin-interacting protein (TXNIP) expression in rats with acute cerebral infarction.Methods A total of 48 Sprague-Dawley rats were randomly divided into sham-operation group, model group, negative control group, and TXNIP interference group. A rat model of ischemia-reperfusion injury was established. On day 3 of modeling, neurological score was evaluated and cerebral infarct area and nerve cell apoptosis were measured, as well as the mRNA expression of TXNIP and the protein expression of TXNIP, ASK1, p-ASK1, and caspase-1 in brain tissue.Results On day 3 of modeling, the TXNIP interference group had a significantly lower neurological score than the model group and the negative control group (1.65±0.10 vs 2.22±0.55/2.49±0.97, F=42.046, P=0.000). Compared with the model group and the negative control group, the interference group had significantly lower cerebral infarct area (16.40%±1.32% vs 24.74%±2.38% and 23.48%±2.72%, F=192.936, P<0.05) and apoptosis rate of nerve cells (22.61%±2.33% vs 71.53%±6.25% and 68.23%±3.05%, F=473.627, P<0.05). Compared with the model group and the negative control group, the interference group had a significantly lower relative mRNA expression level of TXNIP, significantly lower relative protein expression levels of TXNIP, p-ASK1, and caspase-1, and a significantly higher relative protein expression level of ASK1 (P<0.05).Conclusions Downregulation of TXNIP gene expression can reduce cerebral infarct area and nerve cell apoptosis, possibly by inhibiting cell apoptosis mediated by the phosphorylation of the apoptosis-related protein ASK1.