Abstract:[Background] Muskmelon under protected cultivation faces soil deterioration, serious diseases, and the decline of muskmelon yield and quality as a result of continuous cropping and excessive chemical fertilizer and pesticides application. [Objective] This paper aims to clarify the effect of continuous cropping span of muskmelon on soil chemical properties, enzyme activity, and microbial diversity.[Methods] Topsoil samples were collected from the greenhouses after 1 year, 5 years, and 10 years of continuous muskmelon cropping. Soil chemical properties, enzyme activity, culturable microorganism count, and microbial diversity were determined with conventional methods, enzyme assay kits, dilution-plate method, and Illumina Miseq, respectively.[Results] Continuous cropping increased soil total nitrogen, available nitrogen, available phosphorus, and pH. The total nitrogen, available nitrogen, available phosphorus, and pH in soil after 5 years of continuous cropping were 1.04%, 0.56%, 6.00%, and 4.45% higher than those in soil after one year of planting, respectively, and the corresponding figures for soil after 10 years of continuous cropping were 7.25%, 6.86%, 17.75%, and 5.60%, respectively. However, soil available potassium was reduced significantly with the continuous cropping and the reduction reached 12.68% in soil after 10 years of continuous cropping. Continuous cropping significantly decreased the activity of soil urease, alkaline phosphatase, and sucrase, and the decrease was 2.79%, 41.05%, and 38.81% for soil under 5 years of continuous cropping, respectively, and 23.43%, 42.30% and 66.21% for soil under 10 years of continuous cropping, respectively. However, the activity of catalase reduced first and then rose with the continuous cropping. The counts of bacteria and actinomyces decreased significantly with the continuous cropping. To be specific, the number of bacteria, actinomyces, and fungi was 6.02%, 29.32%, and 32.50% smaller in soil after 5 years of continuous cropping, respectively, and 58.65%, 53.17%, and 33.75% smaller in soil after 10 years of continuous cropping, respectively, than that in soil after one year of planting. Moreover, bacterial diversity was lowered, as manifested by the reduction of the dominant Proteobacteria and Bacteroidetes and the beneficial Rhizobium, Pseudomonas, and Bacillus. The abundance of fungi was increased and the evenness was reduced. Specifically, the abundance of Ascomycota rose. Redundancy analysis indicated that soil total nitrogen, available nitrogen, available phosphorus, and pH and soil Sphingomonas, Gemmatimonas, and Mycothermus were in positive correlation with continuous cropping span. [Conclusion] Continuous cropping of muskmelon resulted in deterioration of soil chemical properties and microbial environment. The study provided a reference for the remediation of soil under continuous muskmelon cropping and sustainable development of muskmelon industry.