Objective Herba Patriniae is a root grass of perennial herbaceous plants in the family Caprifoliaceae, with various pharmacological activities. This study was conducted to investigate the protective effect of Herba Patriniae on paracetamol-induced liver injury in rats. Methods Rats were intravenously injected with acetaminophen and then randomly divided into the control, model, low-dose Herba Patriniae, medium-dose Herba Patriniae, high-dose Herba Patriniae and bifendatatum groups. The low-, medium- and high-dose Herba Patriniae groups were gavaged with 4, 8 and 16 g / kg Herba Patriniae once per day, respectively. The bifendatatum group received 0. 3 g / kg bifendatatum, and the control and model groups were given the same amount of normal saline for 30 consecutive days. The liver index was calculated. Hematoxylin and eosin staining was used to detect the degree of pathological injury to the liver tissue. Serum ALT, AST and ALP levels were detected using kits. Tumor necrosis factor-α ( TNF-α), interleukin-6 ( IL-6) and interleukin-1β ( IL-1β) were determined via enzyme-linked immunosorbent assay. Superoxide dismutase (SOD), MDA and GSH-Px contents in the liver homogenate were detected using kits. Results Compared with those of the control group, the liver index of the model group was significantly increased, the AST, ALT, ALP, TNF-α, IL-6 and IL-1β levels were significantly increased, the SOD and GSH-Px contents were significantly reduced, and the MDA content was significantly increased (all P<0. 05). Compared with those of the model group, the liver indexes of the Herba Patriniae and bifendatatum groups were significantly reduced, the degree of pathological damage was significantly attenuated, the AST, ALT, ALP, TNF-α, IL-6 and IL-1β levels were significantly decreased, the SOD and GSH-Px contents were significantly increased, and the MDA content was significantly decreased (all P<0. 05). Conclusions Herba Patriniae protected rats from paracetamol-induced liver injury by alleviating pathological injury to the liver tissue, inhibiting the release of inflammatory factors and relieving oxidative stress.