--- - |2 Summary Acute kidney injury (AKI) occurs in 5% of hospitalized patients and in 50% of sepsis patients with acute renal dysfunction. However, there have been no safe and effective therapeutic strategies. The hypoxia condition is closely related to renal injury and function under AKI. As hypoxia‐inducible factor 1α (HIF‐1α) is critical for the cellular response to hypoxia, we investigated the protective effect of HIF‐1α in a rat AKI model. We found that HIF‐1α injection improved the survival of rat with AKI, and the level of creatinine and blood urea nitrogen (BUN) was also increased. Our data showed that HIF‐1α treatment significantly alleviated ischaemic/reperfusion injury to kidney tubules and nephrocytes. We also found the downstream factors, such as EPOR, VEGF, and PHD3, were also upregulated by HIF‐1α. Finally, it was observed that HIF‐1α treatment also increased the percentage of adult resident progenitor cells (ARPC) in vitro and in vivo. In conclusion, HIF‐1α plays a protective role in the ischaemic AKI model through stimulating the proliferation of ARPC, and our study provided a potential therapeutic strategy for AKI. - Clinical and Experimental Pharmacology and Physiology, Volume 45, Issue 10, Page 1076-1082, October 2018.