The objective of this study was to characterize the changes of soil enzyme activities and soil microbe population as related to mineral fertilizer and crop residues based on a long-term field experiment. The experiment, initiated in 1986, has three treatments: unfertilized (CK), mineral fertilizer alone (MF) and rice residues plus mineral fertilizer (RF). The cropping system consists of barley (Hordaum vulgare L.), early rice, and late rice, three crops in a year. In May 2013, after early and late rice transplanting, soil samples were collected from the 0-20 cm layers to determine soil enzyme activities and soil microbe population. The results indicated that during the rice growing seasons, the enzyme activities were significantly affected by application of crop residue and mineral fertilizer practices: they were greater in the MF and RF than in the CK and were similar during the early and late rice season. The b-glucosidase and alkaline phosphatase activities reached peak values at the tillering stage and booting stage after crop residue and mineral fertilizer application, respectively, and gradually decreased up to the maturity stage. Arylsulfatase and arylamidase activities reached peak values at the maturity stage. Combined application of crop residue and mineral fertilizer also improved the numbers of aerobic bacterial, actinomycete and fungus, but the improvement by mineral fertilizer alone was limited. Under the intensive rice-rice-barley cropping system, joint application of crop residue and chemical fertilizer improved soil enzyme activities and soil microbe population, but the change of soil enzyme activities and soil microbe population from chemical fertilizer alone was not significant.