Abstract: Rehmannia glutinosa L. is one of Chinese herbal medicines with serious cultivation obstacles. In this study, samples of newly cultivated and continuously cropped R. glutinosa soil and uncultivated soil were collected in R. glutinosa genuine producing area in Jiaozuo City of Henan Province and R. glutinosa production area in Linfen City of Shanxi Province. R. glutinosa samples also were collected from the same areas. The soil samples were then evaluated in relation to R. glutinosa quality under continuous cropping, and R. glutinosa quality decline mechanisms were explored in terms of soil micro-ecological (soil microbes and enzyme) activities. The results showed that R. glutinosa quality in the genuine producing area was significantly different (P<0.05) from that in the production area. However, the quality differences of R. glutinosa between newly cultivation and continuous cropping were significantly higher than those between different producing areas. Continuous cropping in the two areas significantly inhibited R. glutinosa seedling growth. While continuous cropping reduced the number of rhizosphere bacteria, it increased fungi and actinomycetes populations. This resulted in the transition from bacteria-populated to fungi-populated soil type. Compared with newly cultivated R. glutinosa soil, continuously cropped R. glutinosa soil significantly decreased the activities of urease, sucrase and catalase (P < 0.05) while slightly increased the activities of polyphenoloxidase, cellulose and protease in the two areas. However, phosphatase activity in continuously cropped R. glutinosa soil exhibited the opposite trend for the two areas. Therefore, speculation was put forward that auto-toxicity changed the soil micro-ecology and somehow affected soil enzyme activity, thereby reducing R. glutinosa ability to absorb nutrients.