Cotton is considered as one of the most important crops in Egypt. Measuring the leaf area of such plant is one of the most accurate indicators to estimate the quantity of pesticides and productivity. Several research  works have shown that deriving mathematical models as a method  to estimate the leaf area of various plants is considered more precise, time- saving, cost-reducing and less harmful on the examined plants compared to direct methods of measuring leaf area such as digital planimeter, electronic devices and manual engineering measuring tools. In spite of all this developing mathematical models in the field of determining Egyptian cotton leaves area has not attained the least of research work. Therefore, the aim of the study is deriving a mathematical model suitable for predicting the area of cotton leaves. To achieve this aim, a mathematical model was developed using 240 Egyptian cotton leaves (Giza 86). These leaves were collected at random from different heights and different fields in Kafer El-Dawar centre, El-Behera Governorate, Egypt. Regression analysis has been used in developing 19 mathematical models to choose the best model for predicting leaf area through calculating statistical indicators that included: R², root mean square error and mean absolute error. The selected models have been mathematically analyzed to obtain the regression constants of each model. Data analysis has shown that the best model is the one that determined the actual area of the leaf area. The outcome equation is as follows:   Where (LA) is the leaf area (cm²) and the rest of dimensions are measured in centimeters. The efficiency of this model has been tested by defining R² and comparing predicted leaf area results from the model with measured leaf area results. The results have shown that the developed model mentioned above is the most accurate model to be recommended in estimating Egyptian cotton leaves area from leaf width (W), main lobe length (L), right lobe length (L1) and left lobe length (L2). The developed regression model can be considered an alternative method to determine the Egyptian cotton leaves area instead of the direct method represented by for example the leaf area measuring instrument.