Due to its selectivity and sensitivity, capillary electrophoresis coupled to laser-induced fluorescence has evolved as a useful analytical tool for determining drugs in biological samples. This paper describes a simple, sensitive, efficient, and rapid method for analyzing propranolol without derivatization in plasma by CE-LIF using a diode solid-state laser at 266nm. An experimental design methodology was assessed for the investigation of electrophoretic parameters and a Box-Behnken design was selected to optimize both sensitivity and efficiency. The CE-LIF method was linear over the concentration range of 50–850ngmL −1 and successfully applied to a real forensic sample.