Objective: To analyze the effects of Ligustrazine hydrochloride injection combined with piracetam on hemorheology and serum levels of related cytokines in patients with acute cerebral infarction (ACI). Methods: A retrospective study was conducted on 94 patients with ACI admitted to Our hospital from May 2021 to April 2024. They were divided into a reference group and a combined group according to different treatment plans, each with 47 cases.The reference group received piracetam treatment, while the combined group received piracetam + Ligustrazine hydrochloride injection treatment. The clinical efficacy and safety of the two groups were compared, as well as the National Institutes of Health Stroke Scale (NIHSS), Stroke-Specific Quality of Life Scale (SS-QOL), plasma viscosity, erythrocyte sedimentation rate (ESR), whole blood viscosity high shear, whole blood viscosity low shear, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), neuron-specific enolase (NSE), homocysteine (Hcy), hypoxia-inducible factor-1α (HIF-1α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels before and after 14 days of treatment. Results: The clinical efficacy observed was 93.62%, which was higher than the reference group's 78.72% (P<0.05). Compared with the reference group, the NIHSS score was lower and the SS-QOL score was higher in the combined group after treatment (P<0.05). After treatment, the levels of whole blood viscosity low shear, ESR, whole blood viscosity high shear, and plasma viscosity in the combined group were lower than those in the reference group (P<0.05). After treatment, the levels of IL-6, Hcy, HIF-1α, MDA, and MCP-1 in the combined group were lower than those in the reference group, while the levels of NSE and SOD were higher than those in the reference group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: The combination of Ligustrazine hydrochloride injection and piracetam has significant therapeutic effects on ACI, improving hemorheology, inhibiting inflammation, alleviating nerve damage, and promoting the recovery of quality of life. It has good safety.