Diabetes Mellitus (DM) is often recognized through an increase in a person's blood sugar level. Factors that can affect the increase in blood sugar levels of DM patients one of which is cholesterol. It usually contains the bookkeeping of several types of cholesterol, including LDL and total cholesterol. DM data are assumed to experience heterokedasticity so that in this study analyzed using regression of weighted cubic spline nonparametric. The estimation method used is weighted least square (WLS). This study aims to obtain a weighted cubic spline model on cholesterol based DM data. The selection of the best model can be seen based on the criteria for the value of generalized cross validation (GCV) minimum. Based on the analysis obtained weighted cubic spline models for cholesterol factors for blood sugar as follows: