This article describes an effective microchip capillary-electrophoresis protocol for rapid and effective measurements of food-related seleno amino acids, including Se-methionine (Se-Met), Se-ethionine (Se-Eth), Se-methyl cysteine (Se-Cys), utilizing o-phtaldialdeyde/2-mercaptoethanol (OPA/2-ME) derivatization. Relevant parameters of the chip separation and amperometric detection are examined and optimized using a response surface methodology (RSM). Under optimum conditions, the analytes could be separated and detected in a 30 mM borate buffer (pH 9.3, with 28 mM sodium dodecul sulfate) within 300 s using a separation voltage of 2000V and a detection voltage of +0.9 V. Linear calibration plots are observed for micromolar concentrations of the Se-amino acid compounds. The negligible sample volumes used in the microchip procedure obviates surface fouling common to amperometric measurements of selenoamino-acid compounds. The new microchip protocol offers great promise for a wide range of food applications requiring fast measurements and negligible sample consumption.