In order to explore the efficacy of nanoantibiotics in rats with sepsis based on MicroRNA-195 and TGF-β1/Smads signaling pathway, a total of 160 Wistar rats with sepsis were selected and randomly divided into 4 groups of general antibiotics (GA) treatment group and nanoantibiotics treatment (NT) group, MicroRNA-195 treatment (MT) group and TGF-β1/Smads (TS) treatment group with 40 sepsis rates in each group. After each group was treated for 24 hours, the supernatant was centrifuged, the enzyme-labeled reagent was added to sample wall, the absorbance value of each well in sequence was measured, and the linear regression equation of the standard curve was calculated based on the concentration and absorbance value of the standard. Before and after the experiment, the changes in body weight, mental state, activity, respiration, and abdominal cavity of species rats in each group were observed and measured; the expression of Interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), TGF-β1, Smad2, Smad3, Smad7 were recorded and analyzed. The results showed that the expression levels of IL-1, TNF-α, TGF-β1, Smad2, Smad3 and Smad7 in sepsis rats in GA group were higher than those in the NT group (P < 0.05); the myocardial cells in MT group were significantly smaller and the cell arrangement was tighter and more orderly than those in TS group; and the expression levels of TNF-α, IL-6, TGF-β1, Smad2, Smad3, and Smad7 were significantly reduced (P < 0.05). In summary, the MicroRNA-195 and TGF-β1/Smads may promote cardiac remodeling in sepsis rats by up-regulating the nanoantibiotics signaling transduction pathway, thereby having objective curative effect on sepsis rats. The study results of this paper provide a reference for further research on the efficacy of nanoantibiotics in sepsis rats based on MicroRNA-195 and TGF-β1/Smads signaling pathway.