Objective: Acute hyperosmolality can lead to hyperkalemia, chronic hyperosmolality to K⁺-depleted states, being of clinical importance, especially for patients with diabetes. The hyperkalemia is known to be based on a disturbed electrolyte distribution between intra- and extracellular spaces. This is believed to be caused by passive losses of K⁺ due to cell shrinkage, but extracellular volume increase should dilute [K+]e. Hence, pure passive behaviour might not be sufficient to explain hyperkalemia. We tested whether K⁺- release is mediated by active cellular mechanisms. Methods: Based on measured membrane potentials of muscle fibers at different osmolalities and values for intra- and extracellular ion concentrations and conductances from the literature, we implemented an system identification approach to find a suitable mathematical model structure, that reproduced predicted changes of [K+]e. Computer modelling and simulations were realized with Matlab (The Mathworks, Inc.). Results: [K+]e is mainly affected by the sensitivity of the Na/K-ATPase (NKA) for [Na+]i and [K+]e, the maximum NKA activity and the Na⁺-conductance (g_Na) of cells. The NKA evokes its effects on [K+]e by its pump activity directly, wheres g_Na acts indirectly via its depolarizing impact, leading to an increased K⁺ outward current. Interestingly, K⁺ conductances have only minor influence on [K+]e. Upon raising extracellular osmolality, muscle cells shrink, thereby diluting [K+]e. This is prevented by the activation of Na/K/2Cl-cotransporters (NKCC), which depolarize muscle cells and thereby increase K⁺ outflux. Conclusion: If the model behaved completely passive upon hyperosmotic challenges, [K+]e should decline not raise. The increased muscular K⁺-release observed during hyperosmotic states can be explained by the activation of transport processes, that have direct or indirect depolarizing effects on the membrane potential. This could be attributed to the NKCC of skeletal muscle.