【Objective】To study the effects of notoginsenoside R1 on the levels of intercellular adhesion molecule- 1（ICAM- 1），tumor necrosis factor- α （TNF- α），metalloproteinase- 2 （MMP- 2） and metalloproteinase- 2 inhibitor （TIMP- 2）in rats with atrial fibrillation in order to explore the mechanism of notoginsenoside R1 on the preventing and treating atrial fibrillation. 【Methods】 102 rats were randomly divided into control group ，atrial fibrillation group and notoginsenoside R1 group，with 34 rats in each group. The rat model of atrial fibrillation was established by injection of acetylcholine-calcium chloride into the tail vein. The rats in the notoginsenoside R1 group were intraperitoneally injected with 2 mL of notoginsenoside R1. ECG was used to measure the duration of atrial fibrillation. Masson staining was used to observe the degree of myocardial fibrosis. Immunohistochemistry was used to detect the expression of MMP-2 and TIMP-2 in atrial tissue. The serum ICAM-1，TNF-α，MMP-2 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay（ELISA）. The levels of ICAM-1，TNF-α and type I collagen in atrial tissue were determined by Western blotting.【Results】Before the treatment of notoginsenoside R1 ，there was no significant difference in the duration of atrial fibrillation between the two groups（P > 0.05）. After treatment，the duration of atrial fibrillation in the notoginsenoside R1 group［（6.37±2.02）s］was lower than that in the pre-treatment and the atrial fibrillation groups（P < 0.05）. Masson staining showed：the amount of atrial fibrillar collagen fibers in control group was normal；a large number of collagen fibers were seen in the atrial myocytes of atrial fibrillation group；the patchy and punctate collagen fibers were seen in the atrial myocytes of notoginsenoside R1 group. Compared with control group，the serum levels of ICAM-1，TNF- α and MMP-2 ［（137.52±16.59）10-6 g/L，（14.25±1.08）10-6 g/L，（435.26±17.63）10-9 g/L；（109.25±14.62）10-6 g/L ，（12.31±1.27）10-6 g/L， （288.47±15.52）10-9 g/L］were increased（P < 0.05），the serum levels of TIMP-2 levels［（3 541.27±331.24）10-9 g/L ； （3 975.46 ± 313.24）10- 9 g/L］was decreased（P < 0.05），the atrial tissue ICAM- 1，TNF- α and type I collagen levels （0.23±0.07 ，0.51±0.09 、0.63±0.14 ；0.15±0.06 ，0.22±0.07 ，0.27±0.12）were increased（P < 0.05），the atrial tissue MMP-2 protein optical density（0.35±0.07；0.18±0.06）was increased（P < 0.05），the atrial tissue TIMP-2 protein optical density（0.11±0.04；0.18±0.03）was decreased（P < 0.05）in atrial fibrillation group and the notoginsenoside R1 group； Compared with atrial fibrillation group，the levels of serum ICAM-1，TNF- α and MMP-2 were decreased（P < 0.05）， the levels of serum TIMP-2 was increased（P < 0.05），the atrial tissue ICAM- 1 ，TNF- α and type I collagen levels were decreased（P < 0.05），the density of MMP-2 protein in atrial tissue was decreased（P < 0.05），and the optical density of TIMP-2 protein in atrial tissue was increased（P < 0.05）in the rats in notoginsenoside R1 group.【Conclusion】 Notoginsenoside R1 can prevent and treat atrial fibrillation by reducing the levels of ICAM- 1，TNF- α and MMP-2 and increasing the levels of TIMP-2 in serum and atrial tissue of rats with atrial fibrillation.