A piperazine derivartive represented by the following formula: ##STR1## wherein R.sub.1 : an indolyl group which may optionally be substituted by one or more lower alkyl and/or lower alkoxy groups, naphthyl group which may optionally be saturated partially with 2 or 4 hydrogen atoms, or phenyl or cyclohexyl group which may optionally be substituted by one or more lower alkyl groups;A: a single bond or alkylene group;P: a single bond or vinylene group;Q: an -O-alkylene group or -NH-alkylene group when P is a single bond, or a single bond when P is a vinylene group; andR.sub.2 : a lower alkyl, morpholino-lower alkyl, morpholino-carbonyl lower alkyl, piperidinocarbonyl lower alkyl, piperazinocarbonyl lower alkyl or lower alkylaminocarbonyl lower alkyl group, or an acid addition salt thereof is a proteolytic enzyme inhibitor.