It's believed to be the first time the wife of an al-Qaida official has issued a statement in support of militant operations.
In the past, women have been asked to assist their male relatives, donate money and raise their male children as jihadis. But in each case, the women were encouraged by males.
Al-Zawahiri is known to release video messages through the Internet, but the recent message is reportedly the first posting from his wife.
"Fighting is not easy for women, because she needs a male guardian at her side," Umaima Hassan reportedly said in her message.
Authorities have not been able to authenticate the message's validity.
"For some reason they have decided to tap a resource that heretofore they have tiptoed around ... participation by women in combat operations and suicide bombings," said Evan Kohlmann, NBC News counterterrorism analyst.
Kohlmann said Hasan wrote specifically of "martydom" and "how many sisters carried out a martyrdom operation in Palestine, Iraq and Chechnya, and caused the enemy high costs and caused the enemy a big defeat. We ask from Allah to accept them and connect us with them with goodness."
By asking women to participate in the fight, Kohlmann said, Hasan was asking that women go to combat zones. Kohlmann said it was possible that al-Qaida was facing a personnel shortfall in combat operations.