"Not guilty, Your Honour," Stanisic said after each of ten counts read to him by Judge Carmel Agius.
Stanisic requested to present his own defence at the initial appearance, so he was not assigned ad hoc counsel.
Stanisic, 51, is charged on the basis of individual and command responsibility for prosecution, extermination, murder, torture and deportation of Bosnian Muslims, Croats and other non-Serbs in 1992 when Bosnian Serb forces carried out most of their ethnic cleansing campaign in what is now Republika Srpska.
He is charged with seven counts of crimes against humanity and three counts of violations of the laws and customs of war.
The indictment says that Stanisic, in his capacity as minister of the Bosnian Serb police from April 1 until December 31, 1992, was one of the key participants in a joint criminal enterprise the aim of which was to permanently remove and ethnically cleanse Bosnian Muslims, Croats and other non-Serbs from the territory of the planned Serb state by the commission of crimes.