Abstract: A physiologically acceptable insulin derivative has the terminal amino group of the B chain (B.sub.1, phenylalanine) protected by an acyl group or other blocking group containing up to 7 carbon atoms and the amino group of the A chain (A.sub.1, glycine) is either free or protected by means of an acyl or other blocking group containing no more than four carbon atoms and preferably no more than three atoms other than hydrogen. Pharmaceutical preparations may be prepared containing an effective amount of such an insulin derivative together with a physiologically acceptable diluent. An insulin derivative of reduced antigenicity is obtainable from porcine or bovine insulin by reacting the insulin with an acylating agent or other blocking reagent to acylate or otherwise block the amino group of the B.sub.1 amino acid and optionally block the A.sub.1 and/or B.sub.29 amino acid, followed by purification of the derivative by various methods.