The Virgen de Guadalupe is the Southwestern Catholic equivalent of the Virgin Mary, and is said to have appeared to a peasant along the banks of the Guadalupe River. Anaya's story, which takes place in New Mexico in the 1940s, has characters which venerate the Virgen de Guadalupe, as residents in that area currently do, and his book is full of references to her.
This starts in chapter one, where Antonio sees the Virgen carrying Ultima's owl up to heaven. It answers a difficult spiritual question for him: What happens to baby's who have not been baptized and therefore forgiven for their natural sins? The Virgen carries them to heaven instead of "Limbo" which more strict Catholics of that time believed.
So the Virgen is really a native saint, with dark features, who was said to have spoken the native language. It is one of many ways in which Bless Me, Ultima portrays the mix between Spanish Catholicism and native ways and beliefs. Ultima herself is another way.