[Abstract] Cell membrane permeability (P) governs the molecules or ions to transport through the cell membrane. In this study, we measured P of ruminal microbes in different initial levels of surface tension (ST) and specific surface area (SSA). Data of P in present study and published data of pH, ammonia concentration, digestibility of neutral detergent fibre and gas production in two time scales (tk and ′tk) as input variables Vq(tk) were took into consideration for developing a predictive model. The ideas of Box–Jenkins Operators and Covariance Perturbation Theory Operators were used for the first time to establish a model to predict the variations of cellular permeability. The best model presented sensitivity, specificity and accuracy of > 0.89, and MCC > 0.78 for 77,781 cases (training + validation series). In addition, we also reported a simulation of ternary phase diagram with predicted values of cell permeability at various experimental conditions. ; National Natural Science Foundation of China (Grant No. 31172234) ; Chinese Academy of Science and Technology Strategic Pilot Project (Grant No. XDA05020700) ; Hunan Provincial Natural Science Foundation of China (Grant No. 12JJ3015) ; “Galician Network for Colorectal Cancer Research (REGICC)” (Ref. R2014/039)