Aims: Previous studies have demonstrated that oxidative stress is closely associated with cardiac arrhythmias via altering electrical activity and intra-cellular calcium dynamics of cardiac myocytes. This study aimed to develop a cell computational model to reveal the molecular mechanisms of cardiac arrhythmias induced by oxidative stress. Methods: The present study developed a human atrial cell model includ-ing effects of oxidative stress by incorporating reactive oxygen species (ROS)-induced CaMKII activation and its downstream effects on different ionic channels. The CaMKII dynamics was mimicked by a novel 6-state Markov chain model, including both autophosphorylation and oxidation pathways of CaMKII activation. The effects of activated CaMKII on L-type Ca2+ channels (LCCs), sodium channels and other channels was simu-lated based on previous approaches developed by O’hara et al. and incorpo-rated ryanodine receptors (RyRs) and phospholamban (PLB) from Soltis at el.. Results: Simulation results show that highly activated CaMKII by mas-sive ROS phosphorylated L-type Ca2+ current (ICaL) and elevated intracellular calcium concentration, which eventually resulted in calcium overload in sar-coplasmic reticulum in the condition of oxidative stress. Meanwhile, calcium overload resulted in increase of calcium release and cytoplasmic calcium concentration, which triggered afterdepolarizations (DADs) by increasing the calcium extrusion via the Na+-Ca2+ exchanger (NCX) current. Conclusion: This study reveals effects of massive ROS on calcium cy-cling in atrial myocytes and shed lights on mechanisms of cardiac arrhyth-mias induced by oxidative stress.