Objective To study the effect of geniposide on expression of IL-6, TNF-α, and IL-1β in mammary glands and mammary epithelial cells of mastitic mice. Methods Forty female mice after childbirth were randomly divided into blank control, model, L, M, and H groups. At 12 h after modeling, the L group was treated with low-dose geniposide, the M group was administered intermediate-dose geniposide, the H group was treated with high-dose geniposide, and blank control and model groups were administered an equal amount of phosphate-buffered saline. At 24 h after modeling, the treatment effects were observed. Results mRNA expressions of TNF-α, IL-1β, and IL-6 in model, L, M, and H groups were significantly higher than that in the blank control group ( P < 0. 05). Expressions of TNF-α,IL-1β, and IL-6 mRNAs in the L, M, and H groups were significantly lower than that in the model group ( P < 0. 05). Expressions of TNF-α, IL-1β, and IL-6 mRNAs in M and H groups were significantly lower than that in the L group ( P <0. 05). mRNA expressions of TNF-α, IL-1β, and IL-6 in the M group were significantly lower than that in M and L groups ( P < 0. 05). The levels of TNF-α, IL-1β, and IL-6 in L, M, and H groups were significantly lower than those in the model group ( P < 0. 05). The levels of TNF-α, IL-1β, and IL-6 in M and H groups were significantly lower than those in the L group ( P < 0. 05). The levels of TNF-α, IL-1β, and IL-6 in the H group were significantly lower than those in M and L groups ( P < 0. 05). Conclusions Geniposide inhibits lipopolysaccharide-induced mammary gland inflammation and reduces the levels of proinflammatory factors TNF-α, IL-1β, and IL-6.