Objective To clarify the toxicity reducing mechanism of vinegar-processed Kansui by comparing the plasma metabonomic profiles induced by Kansui and vinegar-process Kansui treatments. Methods Totally 30 SD rats were divided into five groups: controls, 7.875 g/kg Kansui, 15.75 g/kg Kansui, 7.875 g/kg vinegar-processed Kansui and 15.75 g/kg vinegar-processed Kansui. The treatments lasted for 2 weeks. The plasma samples were obtained before, immediately after and 7 days after withdrawal of drugs; the ¹HNMR spectra of each sample were obtained and analyzed by orthogonal partial least-squares-discriminant analysis (OPLS-DA) method. Results Compared with Kansui groups, vinegar-processed Kansui increased plasma lipids, 3-hydrobutyrate and glucose, and decreased the levels of lactate and creatine/creatinine; furthermore, the spectra profiles of vinegar-processed Kansui groups were closer to those of the control group. Seven days after drug withdrawal, the rats of vinegar-processed Kansui groups recovered better than those in Kansui groups. Conclusion Vinegar-processed Kansui has toxicity-reducing effect; it can regulate the metabolism of energy and fat, and reduce the toxicity to the liver and kidney. Plasma metabonomics study based on ¹HNMR spectroscopy and multivariate analysis can be used to explore the toxicity-reducing mechanism of vinegar-processed Kansui.