We tried to develop an efficient strategy to isolate geniposide from Gardenia fruit and use it to treat chronic pain. Eight extraction solvents and three extraction methods were respectively compared with each other for the efficiency of geniposide extraction from Gardenia fruit. Extraction with 80% ethanol under reflux was found to give the highest yield of geniposide. Orthogonal experiment was conducted to optimize the reflux conditions and the optimal conditions are a mass(of Gardenia jasminoides Ellis powder) to volume(of solvent, 80% ethanol) ratio of 1:7 and reflux twice for 60 min each. The geniposide obtained by the reflux method was tested on the rats with chronic constriction injury(CCI) for pain relief. The results show that geniposide can enhance pain threshold and relieve pain via repressing tumor necrosis factor-α(TNF-α) expression in either ipsilateral or contralateral dorsal root ganglion( DRG) cells. These results suggest that geniposide treatement may be an effective clinical method to relieve pain based on the mechanism of molecular biology at DRG due to nerve injury.